Structural Formula A, shown below, and its tautomers represented by Formula B represent a class of potent antimicrobial compounds. Within Formula A and B the variables, e.g. R, R3, and R5 to R9 carry the definitions that follow.

R is hydrogen, or R is C1-C6alkyl, C2-C6alkenyl, (C3-C7cycloalkyl)C0-C4alkyl, (aryl)C0-C4alkyl, or (C2-C6heterocycloalkyl)C0-C2alkyl, each of which is substituted with 0 to 5 substituents independently chosen from halogen, hydroxy, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, mono- and di-C1-C4alkylamino, C2-C4alkanoyl, and C1-C4alkylthio.
R3 is hydrogen, C1-C6alkyl, or C2-C6alkanoyl.
R5 is hydrogen, hydroxy, amino, C1-C2alkyl, C1-C2alkoxy, mono- or di-(C1-C4alkyl)amino, or mono-, di-, or tri-C1-C4alkylhydrazinyl.
R6 is hydrogen, halogen, or amino.
R7 is bromo or R7 is a nitrogen-linked C1-C4alkylamino substituted with a 5 or 6-membered heteroaryl group having 1 or 2 heteroatoms independently chosen from N, O, and S, or substituted with a heterocycloalkyl group, which has 4 to 8 ring members, including 1 or 2 ring heteroatoms independently chosen from N, O, and S.
R7 is a nitrogen-linked heterocycloalkyl or heterocycloalkenyl group, each of which has 4 to 8 ring members, including 0, 1, or 2 additional ring heteroatoms independently chosen from N, O, and S, forming part of a bicyclic system with a 3- to 8-membered cycloalkyl or heterocycloalkyl ring in fused or spiro orientation.
R7 is a nitrogen-linked 6-membered heterocycloalkyl group, 0, 1, or 2 additional ring heteroatoms independently chosen from N, O, and S, and bridged with a methylene or ethylene bridge.
R7 is a group of the formula
optionally attached to a C3-C7 spiro cycloalkyl or a spiro heterocycloalkyl.
RA is hydrogen, or RA is C1-C8alkyl, C2-C6alkenyl, C2-C6alkynyl, C2-C6alkanoyl, (C3-C7cycloalkyl)C0-C4alkyl, (C4-C7cycloalkenyl)C0-C4alkyl, (aryl)C0-C4alkyl, (aryl)(C═O)—, or (C2-C6heterocycloalkyl)C0-C4alkyl, each of which is substituted with 0 to 5 substituents independently chosen from halogen, hydroxy, amino, cyano, nitro, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, mono- and di-C1-C4alkylamino, C2-C4alkanoyl, and C1-C4alkylthio.
RB is hydrogen or C1-C4alkyl.
Each of which R7 is substituted with 0 or 1 or more substituents independently chosen from (a) and 0, 1, or 2 substituents chosen from (b); wherein (a) is chosen from halogen, hydroxy, amino, nitro, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, and C1-C2haloalkoxy, and (b) is oxo, cyano, hydroxyC1-C4alkyl, aminoC1-C4alkyl, C1-C6alkylthio, C2-C6alkanoyl, (mono- or di-C1-C4alkyl)aminoC0-C4alkyl, (C3-C7cycloalkyl)C0-C4alkyl, (C3-C7cycloalkyl)aminoC0-C4alkyl, (C3-C7cycloalkyl)(C1-C4alkyl)aminoC0-C4alkyl, (heterocycloalkyl)C0-C4alkyl, (5-membered heteroaryl)C0-C4alkyl, or (aryl)C0-C4alkyl, where each of (b) other than oxo and cyano is substituted with 0 to 2 substituents independently chosen from halogen, hydroxy, amino, cyano, nitro, oxo, —COOH, —CONH2, C1-C4alkyl, C1-C4alkoxy, mono- and di-(C1-C4alkyl)amino, C1-C2haloalkyl, and C1-C2haloalkoxy.
R8 is C1-C6alkyl, C1-C2haloalkyl, or C3-C7cycloalkyl substituted with 0 or 1 or more halogen atoms.
R9 is C1-C4alkyl, cyclopropyl, or phenyl, each of which is substituted with 0 to 3 substituents independently chosen from halogen, hydroxy, amino, C1-C2alkyl, C1-C2alkoxy, mono- and di-(C1-C2)alkylamino, C1-C2haloalkyl, and C1-C2haloalkoxy.
The synthesis of these compounds has been described previously, in U.S. provisional patent application Ser. No. 11/494,205, filed Jul. 27, 2006, which is hereby incorporated by reference at pages 58 to 76, for its teachings regarding the synthesis of 8-alkoxy-9H-isothiazolo[5,4-b]quinoline-3,4-diones and in U.S. patent application Ser. No. 11/271,556 filed Nov. 10, 2005 which is hereby incorporated by reference at pages 43 to 51, for its teachings regarding the synthesis of 8A,9-dihydro-4aH-isothiazolo[5,4-b]quinoline-3,4-diones.
The previously described synthetic method produces significant amounts of impurities. Additionally the synthesis must be carried out, in part, in DMSO, a reactive and high-boiling solvent. The previously reported method requires chromatographic purification of an intermediate, while the procedure reported here does not require chromatographic purification. Additionally the previously reported method utilizes m-CPBA, a potentially explosive oxidant. Thus, a convenient and efficient synthesis that provides 8-alkoxy-9H-isothiazolo[5,4-b]quinoline-3,4-diones and 8A,9-dihydro-4aH-isothiazolo[5,4-b]quinoline-3,4-diones with reduced production of impurities and side products, and avoids the use of DMSO and m-CPBA is desirable. The present invention fulfills this need and provides additional advantages, which are described herein.